No abstract

The strong association of SSBI, FWT2HL, and PVH with hypertension suggests a common underlying mechanism (presumably small-vessel vasculopathy). The SSBI showed the most significant association for clinical subcortical stroke. The FWT2HL was also a risk factor for the stroke but was less significant than SSBI. The subjects with SSBI should be considered at high risk for clinical subcortical brain infarction or brain hemorrhage.

Aging is related to cognitive decline, and it has been reported that aging disrupts some resting state brain networks. However, most studies have focused on the default mode network and ignored other resting state networks. In this study, we measured resting state activity using fMRI and explored whether cognitive decline with aging is related to disrupted resting state networks. Independent component analysis was used to evaluate functional connectivity. Notably, the connectivity within the salience network that consisted of the bilateral insula and the anterior cingulated cortex decreased with aging; the impairment of functional connectivity was correlated with measured decreases in individual cognitive abilities. Furthermore, certain internetwork connectivities (salience to auditory, default mode to visual, etc.) also decreased with aging. These results suggest that (1) aging affects not only the default mode network but also other networks, specifically the salience network; (2) aging affects internetwork connectivity; and (3) disruption of the salience network is related to cognitive decline in elderly people.

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Unexpected novel events generate an orienting response that plays an important role in some forms of learning and memory. The orienting response involuntarily captures attention and rapidly habituates as events become familiarized. Although evidence from patients with focal lesions and scalp and intracranial event-related brain potential recordings supports the involvement of a distributed neural network involving association cortex and the limbic system in novelty detection, the key neural substrates and temporal dynamics have not been defined. While subjects performed a bi-field visual-selective attention task with random novel stimuli embedded in either attended or unattended visual fields, we measured rapid changes of regional blood oxygenation level-dependent (BOLD) signal to target and novel stimuli using single-trial analysis of event-related functional magnetic resonance imaging with a 4T scanner. Habituation was quantified by serial BOLD signal changes during the first 10 novel stimuli for each subject. Novel stimuli activated the bilateral superior/ middle frontal gyrus, temporal-parietal junction, superior parietal lobe, cingulate gyrus, hippocampus, and fusiform gyrus. The superior/middle frontal gyrus and hippocampus showed significant reduction of BOLD signal during the first few novel stimuli, whereas the signals in the fusiform and cingulate gyrus were constant. Prefrontal and hippocampal responses to attended and unattended novel stimuli were comparably habituated. These results, and previous data from lesion studies, support the view that prefrontal and hippocampal regions are involved in rapid automatic detection and habituation to unexpected environmental events and are key elements of the orienting response in humans.

We studied clinicopathological correlations between magnetic resonance imaging (MRI) appearances of postmortem brains and pathological findings in 12 patients to identify simple criteria with which to distinguish lacunar infarctions from enlarged Virchow-Robin spaces. In vivo MRI was also available for 6 of the 12 patients. We focused on small, silent, focal lesions including lacunar infarctions and enlarged Virchow-Robin spaces that were confirmed pathologically. From a total of 114 lesions, enlarged Virchow-Robin spaces were most often found in the basal ganglia and had a round or linear shape. Lacunar infarctions also were most frequent in the basal ganglia, but 47% of these were wedge-shaped. In the pathological studies, excluding lesions from the lower basal ganglia region, enlarged Virchow-Robin spaces were usually smaller than 2 x 1 mm. The shapes and sizes of the lesions determined by MRI (in vivo and postmortem) concurred with the pathological findings, except that on MRI the lesions appeared to be about 1 mm larger than found in the pathological study. When lesions from the lower basal ganglia and the brain stem regions are excluded, the sensitivity and specificity for discriminating enlarged Virchow-Robin spaces from lacunar infarctions are optimal when their size is 2 x 1 mm or less in the pathological study (79%/75%, respectively), 2 x 2 mm or less in both of the MRI studies: postmortem (81%/90%), and in vivo (86%/91%). In conclusion, we were able to differentiate most lacunar infarctions from enlarged Virchow-Robin spaces on MRI on the basis of their location, shape and size. We stress that size is the most important factor used to discriminate these lesions on MRI.

Previous studies have suggested that intravenous transplantation of mesenchymal stem cells (MSCs) in rat ischemia models reduces ischemia-induced brain damage. Here, we analyzed the expression of neurotrophic factors in transplanted human MSCs and host brain tissue in rat middle cerebral artery occlusion (MCAO) ischemia model. At 1 day after transient MCAO, 3 x 10(6) immortalized human MSC line (B10) cells or PBS was intravenously transplanted. Behavioral tests, infarction volume, and B10 cell migration were investigated at 1, 3, 7, and 14 days after MCAO. The expression of endogenous (rat origin) and exogenous (human origin) neurotrophic factors and cytokines was evaluated by quantitative real-time RT-PCR and Western blot analysis. Compared with PBS controls, rats receiving MSC transplantation showed improved functional recovery and reduced brain infarction volume at 7 and 14 days after MCAO. In MSC-transplanted brain, among many neurotrophic factors, only human insulin-like growth factor 1 (IGF-1) was detected in the core and ischemic border zone at 3 days after MCAO, whereas host cells expressed markedly higher neurotrophic factors (rat origin) than control rats, especially vascular endothelial growth factor (VEGF) at 3 days and epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) at 7 days after MCAO. Intravenously transplanted human MSCs induced functional improvement, reduced infarct volume, and neuroprotection in ischemic rats, possibly by providing IGF-1 and inducing VEGF, EGF, and bFGF neurotrophic factors in host brain.

According to sociometer theory, self-esteem serves as a barometer of the extent to which individuals are socially included or excluded by others. We hypothesized that trait self-esteem would be related to social pain responsiveness, and we used functional magnetic resonance imaging to experimentally investigate this potential relationship. Participants (n = 26) performed a cyberball task, a computerized game of catch during which the participants were excluded from the game. Participants then rated the degree of social pain experienced during both inclusion in and exclusion from the game. Individuals with lower trait self-esteem reported increased social pain relative to individuals with higher trait self-esteem, and such individuals also demonstrated a greater degree of dorsal anterior cingulate cortex activation. A psychophysiological interaction analysis revealed a positive connectivity between the dorsal anterior cingulate and prefrontal cortices for the lower trait self-esteem group, and a corresponding negative connectivity for the higher trait self-esteem group. Heightened dorsal anterior cortex activity and a corresponding connection with the prefrontal cortex might be one possible explanation for the greater levels of social pain observed experienced by individuals with low trait self-esteem.